Downregulation of miR-320a/383-sponge-like long non-coding RNA NLC1-C (narcolepsy candidate-region 1 genes) is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

Cell Death Dis. 2015 Nov 5;6(11):e1960. doi: 10.1038/cddis.2015.267.

Abstract

Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1-C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Embryonal / genetics
  • Carcinoma, Embryonal / metabolism*
  • Carcinoma, Embryonal / pathology
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Down-Regulation
  • Embryonal Carcinoma Stem Cells / metabolism
  • Embryonal Carcinoma Stem Cells / physiology*
  • Humans
  • Infertility, Male / genetics
  • Infertility, Male / metabolism*
  • Infertility, Male / pathology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / metabolism*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Phosphoproteins / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / metabolism
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • Young Adult

Substances

  • MIRN320 microRNA, human
  • MIRN383 microRNA, human
  • MicroRNAs
  • NLC1C lncRNA, human
  • Phosphoproteins
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • nucleolin

Supplementary concepts

  • Testicular Germ Cell Tumor